Screening for p53 mutations in the conserved regions of exons 5-8 was performed in tumors having positive p53 immunohistochemical staining. p53 missense mutations were discovered in 7 of 20 paraffin-embedded uterine sarcomas. Six of the 7 mutations identified were in exon 7 and one in exon 5. All of the mutations were GC to AT transitions, 6 in the coding (non-transcribed) strand and one in the non-coding strand; none was at CpG site. Mutations were detected at condons 148, 241, 242, or 255, not reported hot spots for human or other rodent tumors. The transplantable tumors has same mutation as the primary tumor. Tumors with same mutation from 16 or 17 passages of transplantation originated from the primary-tumor. p53 mutations were found in tumors with positive p53 immunoreactivity in tumor with more than 50% labeled cells. K-ras mutations at codons 12, 13 and 61 were not detected in the neoplasms examined. These data suggest that p tumor suppressor genes play an important role in the development and progression of uterine sarcomas in this model.